Interferon-free regimens overcome the effect of portal hypertension on virologic response

M Mandorfer; K Kozbial; C Freissmuth; P Schwabl; AF Stättermayer; T Reiberger; S Beinhardt; R Schwarzer; M Trauner; A Ferlitsch; H Hofer; M Peck-Radosavljevic; P Ferenci

doi:10.1055/s-0035-1551738

Zeitschrift für Gastroenterologie, Table of Contents

Interferon-free regimens overcome the effect of portal hypertension on virologic response

M Mandorfer ¹, K Kozbial ¹, C Freissmuth ¹, P Schwabl ¹, AF Stättermayer ¹, T Reiberger ¹, S Beinhardt ¹, R Schwarzer ¹, M Trauner ¹, A Ferlitsch ¹, H Hofer ¹, M Peck-Radosavljevic ¹, P Ferenci ¹

¹Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria

Abstract

Background: Clinically significant portal hypertension (CSPH) is the strongest predictor of virologic response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC) and cirrhosis.

Aim: To investigate the impact of portal pressure assessed by hepatic venous pressure gradient (HVPG) measurement on on-treatment response and viral kinetics in patients treated with IFN-free regimens outside of clinical trials.

Methods: Fifty-six patients with CHC and cirrhosis who underwent HVPG measurement before starting an IFN-free therapy were retrospectively studied. CSPH and pronounced portal hypertension (PPH) were defined as HVPG ≥10 mmHg and ≥16 mmHg, respectively. HCV-RNA was assessed using the Abbott RealTime HCV assay (lower limit of quantification (LLOQ) and detection of 12IU/mL).

Results: Thirty-two (57%), 12 (21%) and 11 (20%) patients received sofosbuvir/daclatasvir, sofosbuvir/ribavirin and sofosbuvir/simeprevir, respectively. One (2%) patient was treated with simeprevir/daclatasvir. CSPH and PPH were observed in 41 (73%) and 31 (55%) patients, respectively. The distribution of treatment regimens was comparable between patients with or without CSPH/PPH. Patients with CSPH/PPH had lower platelet counts and albumin levels, while bilirubin levels, INR, MELD and Child-Pugh scores were higher than in patients without CSPH/PPH. At week 4, only 26/53 (49%) and 6/53 (11%) patients had HCV-RNA<LLOQ and undetectable HCV-RNA, respectively. At week 12, undetectable HCV-RNA was achieved in only 43/56 (77%)

patients, while all patients had HCV-RNA<LLOQ. Importantly, on-treatment response and viral kinetics were neither affected by CSPH, nor by PPH at any time point.

Conclusions: This is the first study to demonstrate that IFN-free regimens overcome the negative effect of portal hypertension on on-treatment response and viral kinetics.

The results will be updated prior to the presentation at the meeting to include additional patients as well as preliminary sustained virologic response rates.